The discovery of a small rounded mass or nodule in the lung of a patient, usually by chest radiograph, raises the problem of ascertaining whether the mass is malignant or benign. Inasmuch as a benign nodule is usually left undisturbed whereas a malignant nodule requires immediate aggressive therapy, it becomes important to quickly determine the nature of the nodule.
In the past, surgery with resection of the nodule and subsequent pathological analysis were often performed. However, in the early 1950's, it became apparent that a large number of patients were being exposed to unnecessary surgery. Since indiscriminate surgical exploration of lung nodules led to many unnecessary procedures with their attendant mortality and morbidity, less invasive methods of differentiating between a benign nodule of the lung and a malignant tumor were sought. Various research studies indicated that the percentage of benign nodules in a poplulation of patients with newly discovered nodules varied between 40 and 60%.
In the early 1950's, it was also observed that calcified nodules were almost never malignant. Hence radiographic methods to detect the presence of calcifications in lung nodules were developed, in particular linear tomography which blurs the structures above and below the plane of the nodule and permits a better detection of calcification than standard chest radiography. This method has evolved as the main procedure of non-invasive investigation of lung nodules since the late 1950's to the present time.
Others approached the problem differently, by devising methods to obtain small fragments of tissue from the nodule with less risk than surgery. These methods involve bronchoscopy directed biopsy and percutaneous needle biopsy. Although these methods are less risky than surgery, they all entail a significant morbidity albeit at a much lower mortality.
In the early 1970's, a new method of radiographic investigation, termed computed tomography, was introduced. Briefly, this procedure involves positioning a patient between an X-ray source and radiation detectors such that a fan-shaped or pencil-like X-ray beam which is thin in the axial dirction can be projected through the patient. Rotation or displacement of the X-ray source and detectors relative to the patient, results in the development at the detectors of signals indicative of X-ray transmission characteristics or differences in attenuation of the X-ray beam along a plurality of paths through the patient. From these signals it is possible to calculate and print out or record a distribution or matrix of analogs corresponding to the various elements in the body lying in the path of the X-ray beam having differing radiographic densities.
In the case of scanning a lung nodule an image of a transverse section of the patient' chest or torso containing lung tissue is reconstructed based on the above-noted differences in attentuation of the X-ray beam as measured by the detectors at various angles to the object scanned. Computer programs estimate the attenuation of each portion of space of voxel within the X-ray beam by assigning CT numbers to each voxel. These CT numbers are theoretically scaled to the attenuation of water which is the zero value and pure air which is -1000. The unit of measurement is termed the Hounsfield (H). The success of this method is fundamentally based on the fact that the CT scanner system is able to differentiate differences in radiographic densities of 0.5 to 1% whereas conventional systems separate densities only if they are different by at least 5 to 10%.
Based on the fact that CT scanners were 5 to 20 times more sensitive to density differencs than conventional radiographic techniques and provided an objective measurement with numbers rather than a subjective visual evaluation of density as with standard techniques, the role of quantitative analysis of the computed tomographic data in patients with lung nodules was investigated. A study involving a large series of patients with mathematical analysis of the density numbers of lung nodules showed that CT scanning was more sensitive in differentiating benign from malignant lung nodules than conventional techniques. It was found that above a certain representative CT number, all lung nodules were benign. It was ascertained that among the nodules which were not considered calcified by standard tomography, a significant percentage (60%) were found to be calcified by computed tomography thereby decreasing the number of unnecessary invasive procedures in these patients who would have otherwise been investigated more aggressively.
Despite the success demonstrated by this study with a particular scanner and a particular method of calculating the CT numbers of each nodule, it quickly became apparent that this method could not be directly translated to other scanners. Several investigators attempted to apply the method using the guidelines and results of the original study but were unable to obtain satisfactory results. A complete analytic study of all factors involved in obtaining correct CT numbers for lung nodules revealed that: (1) CT numbers can vary from scanner to scanner for the same object, (2) CT numbers can vary in the same scanner depending upon the spatial position of the lung nodules investigated, (3) CT numbers can vary from day to day for the same object (temporal drift), (5) the technique used (exposure factors, slice thickness) can change the CT numbers, and (6) the dimensions of the patient's chest can also affect the CT density of a nodule. Further analysis demonstrated that these variations were related to the following:
(1) The computer program used by each manufacturer to reconstruct the images introduces variations in the CT numbers of lung nodules even if the scanners are calibrated with standard available state-of-the-art phantoms which are usually manufactured to give the densities of test objects in water or in plastics but not in air. These differences in computer algorithms also explain the differences in CT numbers obtained for nodules of identical composition but different sizes.
(2) The design of the CT scanner, i.e., third generation versus fourth generation, also influences the CT numbers obtained. It may also explain why CT numbers of the same nodule can vary if the nodule is located in different positions within the scanner.
(3) Depending upon the design of the scanner, the changing characteristics of the X-ray beam as the X-ray tube ages will also introduce errors in measuring CT numbers from day to day.
(4) The CT scanner being a complex electronic machine, variations in the performance of each component as well as the sensitivity of the system to temperature and humidity creates temporal drifts which are very difficult to control. All of these factors explain why it is essentially impossible to correlate the experience obtained on one scanner with that of other scanners since the CT numbers of lung nodules are dependent upon several independent variables. Because of these variations, there exists the need for a simple method of determining the CT density of a lung nodule applicable to all scanners.
Inasmuch as many variables affect the measured CT numbers of a lung nodule, it is necessary to use a standard object of reference against which CT scans of patients with lung nodules can be compared to determine whether the lung nodule is likely to be benign or malignant by virtue of its density. Current phantoms are available in a number of variations, some being plastic replicas of the human body or specific portions thereof while others consist of actual human bones cast in plastics. Recently introduced phantoms include a set of reference samples having known attenuation coefficients surrounded by a water medium housed within a plastic vessel. Phantoms used to calibrate computed tomography systems are usually cylindrical discs having a diameter ranging from 20 to 40 cms. These available phantoms, however, do not simulate the patient's chest with a nodule positioned therein to allow their use as a standard reference phantom for the particular problem of a lung nodule.
Accordingly, it is an object of the present invention to provide a phantom or a reference system against which the density of lung nodules can be compared and their density estimated regardless of the variability factors mentioned above.